In order to compare sociodemographical data and preexisting risk medical conditions in patients requiring hospital admission for 2009 pandemic influenza A (H1N1) virus infection and those managed on an outpatient basis, a prospective observational, matched case-control study in 36 hospitals of the Spanish National Health Service was conducted from July 2009 to February 2010. Cases were patients aged 6 months to 18 years hospitalized for influenza syndrome, in whom 2009 influenza A (H1N1) virus infection was confirmed using real-time reverse-transcription polymerase chain reaction. Controls were patients aged 6 months to 18 years with confirmed 2009 influenza A (H1N1) infection managed on an outpatient basis. There were 195 cases and 184 controls. In a multivariate model, hospitalization was more frequent in children aged <2 years (odds ratio (OR), 13.8; 95% confidence interval (CI), 1.7-106.4), those with neurological and/or neuromuscular diseases (OR, 3.0; 95% CI, 1.1-8.2), and those whose parents had less than a secondary educational level (OR, 2.7; 95% CI, 1.4-5.2). Children aged <2 years, children with neurological diseases, and children from families with a lower educational status had a higher risk of hospitalization due to influenza A (H1N1) 2009 infection.